Study uncovers a hidden trigger behind dangerous heart rhythms

Scientists have identified an unexpected weak point in the heart's electrical system that may help explain a rare but dangerous rhythm disorder. The finding suggests a potential treatment target beyond the channels that usually attract the most attention.

Researchers at The Ohio State University examined a faulty form of calmodulin, a small protein that helps regulate the heartbeat. Their experiments showed that the defect can allow an unusual influx of sodium into heart cells, disrupting the signals that keep contractions coordinated.

The study, published in the Journal of Clinical Investigation, used cell experiments and genetically modified mice. It clarifies one inherited condition, but it does not explain all irregular heartbeats.

Every heartbeat relies on precisely timed movement of electrically charged particles, including sodium and calcium. Tiny openings known as ion channels let these particles cross cell membranes, generating electrical signals and helping initiate contraction.

Calmodulin plays a key role in controlling that process. Rare mutations in the genes that produce it can lead to severe rhythm disturbances, sometimes affecting children and young adults whose symptoms are difficult to manage.

The team focused on a specific mutation called D96V. Earlier research connected defective calmodulin to impaired calcium channels, but that explanation did not fully account for the electrical disturbance associated with this protein variant.

The researchers found that another factor was involved: a sodium channel called NaV1.6. Although it is less abundant in heart cells than the main cardiac sodium channel, its position makes it especially important in this disorder.

NaV1.6 sits near structures that release calcium inside the cell. When the faulty protein keeps the sodium channel from closing properly, sodium continues to enter after it should have stopped, interfering with nearby calcium release.

That extra activity can lengthen the electrical signal and trigger abnormal contractions. In mice, removing NaV1.6 specifically from heart cells protected against the resulting electrical problems, reinforcing evidence that the channel contributes to the disorder.

The result gives researchers a more precise target for treatment. A therapy aimed at the relevant channel could interrupt the faulty signal while avoiding some of the broader effects of less selective approaches.

Still, the study did not produce a new treatment for patients. Scientists must determine whether safely targeting NaV1.6 would provide lasting benefits in people, and whether the same mechanism applies to other rhythm disorders.

For now, the advance offers a more detailed picture of how a small inherited defect can destabilize the heartbeat. That insight could help future therapies address the specific electrical fault rather than only its consequences.

Source: The Ohio State University.